Development and characterization of a PLGA-HA composite material to fabricate 3D-printed scaffolds for bone tissue engineering.

Additive manufacturing is a rising field in bone tissue engineering. Additive fabrication offers reproducibility, high precision and rapid manufacture of custom patient-specific scaffolds. The development of appropriate composite materials for biomedical applications is critical to reach clinical application of these novel biomaterials. In this work, medical grade poly(lactic-co-glycolic) acid (PLGA) was mixed with hydroxyapatite nanoparticles (nHA) to fabricate 3D porous scaffolds by Fused Deposition Modeling. We have first confirmed that the composite material could be printed in a reproductive manner. Physical characterization demonstrated a low degradation of the material during manufacturing steps and an expected loading and homogeneous distribution of nHA. In vitro biodegradation of the scaffolds showed modifications of morphological and physicochemical properties over time. The composite scaffolds were biocompatible and high cell viability was observed in vitro, as well as a maintain of cell proliferation. As expected, the addition of nHA displayed a positive impact on osteodifferentiation in vitro. Furthermore, a limited inflammatory reaction was observed after subcutaneous implantation of the materials in the rat. Overall, this study suggests that this composite material is suitable for bone tissue engineering applications.

PEDOT:PSS electrodes for acute experimental evaluation of vagus nerve stimulation on rodents.

The vagus nerve (VN) is involved in the autonomic regulation of many physiological systems (cardiovascular, respiratory, gastrointestinal, etc.) and its stimulation is already an approved therapy for refractory epilepsy and depression. Other pathologies are thought to be treatable through vagus nerve stimulation (VNS), such as heart failure, cardiac arrhythmia, inflammation or auto-immune diseases. However, the efficacy of the stimulation is not always optimal, partly due to the materials and the architecture of currently available electrodes. Standard electrodes, composed of metallic rings that stimulate the whole diameter of the nerve, are not adapted to experimentations involving spatial selectivity. Efficient and selective charge injection is usually difficult to achieve simultaneously, especially in experimental setups using rodents, due to the thin diameter of their VN. In this paper, we show that we can take advantage of the high charge injection property of conducting polymers to acutely stimulate the vagus nerve in rodents, using individual active electrodes with dimensions $725\,\,\mu \mathrm{m}\times \,450\,\,\mu\mathrm{m}$. A particular PEDOT:PSS architecture integrating 12 active electrodes is developed and applied to the VN of one rat. A closed-loop VNS system developed in our previous works is used to stimulate the VN while analyzing the heart rate response. Results show the feasibility of this kind of electrodes for acute VNS on rodents and open the path towards new experimentations focused on selective stimulation and recording.